Methylation is vital in many biological processes, and potent and specific inhibitors of methyltransferases are valuable tools in understanding these processes. Some positive clinical and preclinical results from DMA methyltransferase inhibitors indicate the potential use of these inhibitors in cancer therapy. In this proposal, we intend to develop a fluorescence polarization assay which is non-radioactive and amenable to high throughput screening. This will greatly facilitate the discovery of novel inhibitors of methyltransferases by high throughput screening. These inhibitors will be not only valuable research tools to study the large family of important enzymes but also initial leads to develop future drugs for cancer and other diseases.